The present invention relates to an apparatus and method for increasing the efficiency of ion transport from ion sources into a multipole ion guide, a quadrupole mass analyzer or a three dimensional ion trap. Multipole ion guides have been effectively used to capture and transport ions which are delivered into vacuum from Atmospheric Pressure Ion (API) sources such as Electrospray (ES) and Atmospheric Pressure Chemical Ionization (APCI). Ions whose mass to charge (m/z) values fall within the stability region of the multipole ion guide are transmitted through the length of the guide and delivered to the entrance region of a mass analyzer. Specifically, the present invention addresses the ion transfer from a multipole ion guide into either a subsequent multipole ion guide such as a quadrupole mass analyzer or a three dimensional ion guide mass analyzer. Atmospheric Pressure Ion Source mass spectrometry (API-MS) has emerged as a sensitive method for detecting sample ion solutions with both discrete sample and on-line sample introduction methods. The invention improves performance with quadrupole mass and ion trap mass spectrometers for both on-line and off-line applications. In addition, the apparatus and methods described can be configured to improve quadrupole and ion trap mass analysis performance with ion sources other than API sources.
Multipole ion guides have been used to efficiently transfer ions through vacuum or partial vacuum into mass analyzers. In particular, multipole ion guides have been configured to transport ions from an Atmospheric Pressure Ion (API) Source through one or more vacuum pumping stages and into a mass analyzer. Quadrupole, magnetic sector, Fourier Transform (FTMS), three dimensional ion trap and Time-Of-Flight (TOF) mass analyzers each have different entrance ion optics criteria which must be satisfied by any ion source ion transport or focusing system. The present invention addresses optimization of the transfer of ions from one multipole ion guide into a subsequent multipole ion guide, quadrupole mass analyzer or a three dimensional quadrupole ion trap. Multipole ion guides and ion traps operate with sinusoidal voltages and separate or combined DC voltages applied to one or more electrodes. The sinusoidal voltage wave forms are usually referred to as AC or RF because the frequency of these wave forms generally fall within the radio frequency range. The combination of AC and DC voltages applied to the rods of a multipole ion guide or the endcaps and ring electrode of a three dimensional quadrupole ion trap can be selected to establish stable ion trajectories for some mass to charge (m/z) values while rejecting others. Mass selection for mass analysis can be achieved in this manner, or ions can be trapped while colliding with background gas to achieve Collisional Induced Dissociation (CID) ion fragments from trapped ions or from ions traversing the length of the ion guide. Ions whose m/z values do not have a stable trajectory for the AC and DC potentials applied to the rods of a multipole ion guide will be rejected from the ion guide before reaching the ion guide exit. The AC and DC voltages applied to the poles of a multipole ion guide can be selected to achieve the functions of selective m/z ion transmission and ion rejection for those ions within the ion guide; however, the fields created by the applied voltages can pose some difficulty for ions trying to enter the ion guide. AC and DC voltages applied to the poles of a commercial analytical quadrupole can reach hundreds of volts and even kilovolt potentials. Similarly, the trajectories of ions attempting to enter a three dimensional quadrupole ion trap are greatly influenced by the RF fields produced from voltages applied to the ring electrode appearing at the ion guide endcap entrance orifice. Ion transport into a multipole ion guide will be considered first.
For a geometrically ideal multipole ion guide, there is no net electric field at the very centerline of the ion guide except for the common DC offset potential applied equally to all ion guide poles. Ions of a given polarity attempting to enter a device whose electrodes have an AC voltage applied can encounter a retarding or rejecting electric field gradient during a portion of the AC voltage phase. Multipole ion guides with an even number of symmetrically spaced parallel poles or rods ideally have no net AC (or RF) field at the centerline or axis of the assembly. Ion beams, however, have a finite cross section and most ions will enter a multipole ion guide such as a quadrupole mass analyzer at some radial distance off the centerline. Consequently, the trajectory of these ions will be influenced by an AC and an asymmetric DC field. Depending on the phase of the AC field, the asymmetric DC field off the centerline and the ion kinetic energy in the axial direction, an approaching ion may successfully enter the ion guide and maintain a stable trajectory, or may be rejected from entering the multipole ion guide or may enter the ion guide with an unstable trajectory. The more time an ion spends in the fringing fields while attempting to enter a multipole ion guide, the more cycles of AC voltage it can be exposed to and thus the more likely that it may be potentially driven into an unfavorable trajectory. For a given average ion energy, the higher an ion m/z value, the lower its velocity. Consequently, the larger the m/z value of an ion, the more time an ion will spend traversing the entrance region of a multipole ion guide while entering the rod assembly. Similarly, if the average ion kinetic energy is reduced, ions of a given m/z value will spend more time traversing the fringing fields of the multipole ion guide as they enter the ion guide. The AC voltages applied to the rods of a multipole ion guide with an even number of poles generally have equal RF amplitude but opposite phase for each adjacent rod or pole. For example, the opposing rods of a quadrupole ion guide have the same phase, which is itself 180 degrees out of phase from the AC voltage applied to each neighboring rod or pole.
One means used to achieve quadrupole mass analyzer m/z selection, is to apply RF and positive and negative polarity DC voltage to the rods with a selected RF to DC amplitude ratio. The DC voltage is equal in amplitude but opposite in polarity on adjacent rods. When quadrupole mass analyzers are scanned in this mass selective mode to acquire a mass spectrum, the AC and DC amplitudes increase proportionally with selected m/z during a scan. Consequently, an ion with a higher m/z value and a slower velocity than a lower m/z value, moves more slowly through the entrance fringing fields and must traverse a higher AC and DC fringing field amplitude in entering the quadrupole in scan mode. Ion transmission efficiency in quadrupole mass analyzers can decrease with increasing m/z, due in part to a decreased efficiency of ions entering the quadrupole. The positive and negative DC voltage components may be added to form a common offset voltage. This DC offset potential can be set to aid in accelerating ions into the quadrupole. In some applications, an additional low amplitude AC wave form, which has a lower frequency than the RF voltage component, is capacitively added to the RF voltage. This additional low amplitude AC voltage of a selected frequency or frequency set is added to the RF voltage to provide resonant frequency excitation for specific ion m/z rejection or fragmentation. With the exception of the DC offset voltage component, the effective AC and DC field strength decreases the closer an ion is positioned to the ion guide centerline. The invention improves the ion transport into a multipole ion guide such as a quadrupole mass analyzer by minimizing the fringing field effects and insuring that ions are delivered close to the multipole ion guide centerline with angular trajectories within the acceptance window of the multipole ion guide.
A quadrupole is the most commonly used multipole ion guide configuration for conducting mass analysis. Quadrupoles can achieve higher mass to charge resolving power compared with hexapoles, octapoles or ion guides with higher numbers of poles. Hexapoles or octapoles have been used in AC or RF only operating mode where ion transport with little or no m/z selection is desired. Hexapoles or octapoles may be used as the ion guide in which Collision Induced Dissociation occurs in what is generically referred to as a triple xe2x80x9cquadrupolexe2x80x9d mass spectrometer. Although the invention can be applied to improve the ion transfer efficiency into any multipole ion guide configured and used in RF only mode, as an ion trap, as a CID region or as a mass filter, a quadrupole will be described as an example. As was described above, ion losses can occur in the entrance region when transferring ions into a quadrupole ion guide or mass analyzers due to the electric fields which influence the ion trajectories as they approach and enter the quadrupole ion guide. Peter H. Dawson (Chapter 2, Quadrupole Mass Spectrometry and Its Applications, Elsevier Scientific Publishing Company, New York, 1976) describes the effective quadrupole mass filter aperture and acceptance for an ion approaching the quadrupole entrance with both AC and DC electric fields applied to the poles. The effective entrance aperture through which ions may enter the quadrupole decreases with increasing resolution, increasing distance from the centerline, and trajectories with increasing off-axis angle and velocity. The success of an ion attempting to enter the quadrupole ion guide at a position off the centerline will be highly dependent on the phase and amplitude of the AC voltage component and the amplitude of the DC voltage component of the applied electric fields. In addition, ions approaching the quadrupole entrance can enter unstable trajectories due to fringing field affects. The more time an ion spends in the quadrupole fringing fields the more chance it has of being driven into an unstable trajectory. Once an ion establishes a stable trajectory in the ion guide, the more RF cycles the ion is exposed to while traversing the quadrupole length, and the higher the mass selection resolution that is achievable. This relationship between maximum resolution achievable as function of the number of RF cycles an ion is exposed to while traversing the length of a quadrupole can be expressed by the empirical relation,
M/xcex94M=(1/K)Nn
(Chapter 6, Dawson). xcex94M is the mass spectral peak width at mass to charge value M for a singly charged ion. N is the number of cycles of the RF field and n and K are constants equal to approximately 2 and 20 respectively. An ion entering with lower axial velocity or energy will be exposed to more RF cycles during the time it spends in the quadrupole than an ion with higher energy. An ion with lower kinetic energy will also spend more time in the fringing fields at the quadrupole entrance and consequently have an increased chance of being driven into an unfavorable trajectory. Various lens configurations have been developed which attempt to overcome these opposing ion entrance and mass analysis criteria to achieve improved quadruple sensitivity and resolution performance. Ideally, it is desirable to introduce ions into a quadrupole ion guide with trajectories parallel to the centerline, with a minimum radial displacement and with a low ion energy.
When transferring ions from one multipole ion guide to another multipole ion guide, as occurs in triple xe2x80x9cquadrupolexe2x80x9d mass analyzers, losses can occur in the interface regions between each multipole ion guide. Commercial triple quadrupole instrument, typically have one or more electrostatic lenses located between two sequential ion guides and are configured not only to minimize the fringing electric fields at the entrance of the downstream ion guide but also to minimize the fringing fields at the exit end of the upstream ion guide. An electrostatic lens element is commonly used at the entrance of a multipole ion guide operated as either a mass analyzer or a Collisionally Induced Dissociation (CID) ion transport region. Commercially available multipole ion guide electrostatic entrance optics have included a flat plate entrance lens with an orifice positioned on the centerline which is located as close as possible along the axis to the entrance face of the multipole ion guide rods to minimize fringing effects. A second commercially available lens, known as a Turner-Kruger lens, has a ground or fixed DC potential entrance face with a tube section projecting into the quadrupole rod assembly. DC voltage is applied to a concentrically positioned inner tube and the DC voltage amplitude is varied proportional to the scanned quadrupole AC and DC voltages during a mass spectrum acquisition. A third commercially available electrostatic entrance lens assembly incorporates the use of a xe2x80x9cleakyxe2x80x9d dielectric material to reduce the quadrupole entrance fringing field effects. A cylindrical lens of semiconductor material is positioned to extend into the entrance region of a quadrupole rod assembly. The xe2x80x9cleakyxe2x80x9d dielectric semiconductor material is positioned to reduce the amplitude of the fringing fields experienced by ions entering the quadrupole assembly. Configurations of one or more flat plate electrostatic lens are commonly used to transfer ions from one multipole ion guide to another. The flat plate lenses are positioned in close proximity to the exit rod face of one multipole ion guide and the entrance rod face of the next multipole ion guide to minimize exit and entrance fringing field effects. The orifice size in these flat plate electrostatic lenses is configured as an optimization of opposing criteria. The smaller the orifice size, the less the fringing field penetration will effect the trajectory of an approaching ion. A larger orifice is desired, however, to avoid interfering with the ion beam cross section and reducing sensitivity. AC only sections or Brubaker lenses have also been added to the entrance and even the exit ends of analytical quadrupoles to reduce the DC fringing field effects for ions entering and exiting the quadrupole. Electrostatic entrance lenses have been configured with Brubaker lenses in commercial quadrupole analyzers to improve the efficiency of ion transport into a multipole ion guide particularly at reduced ion energies.
Each of these multipole ion guide entrance lens configurations help to reduce the effect of fringing fields but have variable ion transfer efficiencies into the ion guide depending on ion energy, ion m/z value, ion angular divergence, the radial position of the ion from the centerline and the AC and DC voltages applied to the ion guide poles. For example, as the resolution is increased for a quadrupole mass analyzer, the radial and angular acceptance window for an ion entering the ion guide may decrease and hence contribute to a reduction in sensitivity during mass analysis. Electrostatic entrance lens configurations do not fully compensate for the variations in entrance conditions encountered with quadrupole ion guide mass analysis operation. The present invention improves the efficiency of ion transport into ion guides by overcoming several of the performance problems encountered when using electrostatic lens systems. The invention improves the efficiency of ion transport into a multipole ion guide by extending the rods of one multipole ion guide into the entrance region of the next multipole ion guide rod assembly. This nested multipole ion guide configuration effectively reduces fringing field losses observed with electrostatic entrance lens configurations.
A second embodiment of the invention improves the ion transfer efficiency from a multipole ion guide into a three dimensional quadrupole ion trap. In this second embodiment, a multipole ion guide of reduced radial dimensions is positioned such that the ion guide rods extend into a counterbore in the entrance end cap of a three dimensional ion trap. The bottom of the counterbore is configured to be the multipole ion guide exit lens or an additional electrostatic lens can be added between the ion guide exit and the end cap. Without the additional electrostatic lens, the end cap aperture at the counterbore bottom serves as the multipole ion guide exit aperture and the ion trap entrance aperture. A portion of the ions unable to enter the ion trap due to rejection by the RF fringing field phase may remain trapped by the ion guide exit region. When the changing ion trap AC phase allows ions to enter the trap by creating a more favorable electric field at the ion trap entrance aperture, the ion guide releases ions into the ion trap. The offset potential of the multipole ion guide can be reduced relative to the three dimensional ion trap end cap voltage to trap ions in the ion guide during ion trap mass analysis. For example if the ion kinetic energy is established by the ion guide DC offset potential, lowering this offset potential below the DC potential set on the ion trap entrance endcap will prevent ions from leaving the ion guide, effectively trapping the ions within the multipole ion guide rod assembly internal volume. The technique of trapping ions in a multipole ion guide using a separate ion guide exit lens potential and releasing ions into a three dimensional ion trap has been described by Douglas in U.S. Pat. No. 5,179,278. Douglas, however, does not teach the configuration of extending the rods of a multipole ion guide into a counterbore of a three dimensional ion trap endcap to improve the trapping efficiency by recapturing ions within the ion guide that have been rejected by the ion trap entrance orifice. The invention also allows the transfer of low energy ions into the three dimensional ion trap, which aids in increasing the trapping efficiency of ions once they enter the ion trap. Also, due to the sharing of the end cap aperture, ions can be efficiently transferred back into the multipole ion guide from the ion trap to achieve improved sensitivity as well as a variety of enhanced scan functions.
A multipole ion guide has been configured with a reduced diameter such that the ion guide with the appropriately shaped exit lens can be positioned inside a larger diameter multipole ion guide. Ions exiting the smaller multipole ion guide pass through the exit lens and are focused to the centerline already inside the larger ion guide. Since the ions leaving the exit lens aperture of the multipole ion guide with reduced dimensions are already inside the larger ion guide, high ion transfer efficiencies can be achieved even with ions having low axial translational energies. Improved mass analysis resolution at higher sensitivities can be achieved with this ion transfer optic when ions are transferred into a quadrupole mass analyzer. The smaller ion guide can be configured to extend continuously through more than one vacuum stages or reside entirely within one vacuum stage. The smaller ion guide can be configured to reside in a different vacuum stage than that of the downstream larger ion guide with the smaller ion guide exit lens serving as the vacuum partition. Alternatively, all multipole ion guides can be configured to reside in the same vacuum pumping stage.
In a second embodiment of the invention, a multipole ion guide with reduced radial dimensions is positioned such that the rods of the multipole ion guide extend into a counterbore of the entrance endcap of a three dimensional quadrupole ion trap. The entrance aperture in the ion trap endcap as serves as the multipole ion guide exit lens. During the ion trap filling cycle, a portion of the ions rejected from entering the entrance aperture of the three dimensional ion trap due to unfavorable RF phase electric fields can be retrapped by the multipole ion guide. Ions ejected out of the entrance endcap by the three dimensional ion trap during mass analysis scanning can also be retrapped by the multipole ion guide. To increase duty cycle and sensitivity, the ion trap endcap voltage can be set higher than the kinetic energy of the ions exiting the multipole ion guide to trap ions in the multipole ion guide during a three dimensional ion trap mass analysis cycle. The multipole ion guide rod potentials can be set to reduce the m/z stability window. In this manner, ions with undesirable m/z values can be ejected from the multipole ion guide and prevented from entering the three dimensional ion trap, thus reducing space charge effects in the ion trap. The multipole ion guide can be configured to extend continuously into more than one vacuum pumping stage.